Basic and Clinical Neuroscience Journal

en Intranasal Delivery of Wharton’s Jelly Mesenchymal Stem Cell-Derived Conditioned Medium in Patients with Alzheimer’s Disease: A Phase 1 Safety and Volum-Escalation Study Cellular and molecular Neuroscience Cellular and molecular Neuroscience Original Original <div style="text-align: justify;">Purpose of the study: Alzheimer's disease is missing proven disease-modifying therapies; Mesenchymal stem cell-derived conditioned medium (MSC-CM) provides a without using living cells anti-inflammatory and neuroprotective strategy. This phase 1 trial examined how safe and acceptable it is to administer intranasal Wharton's jelly MSC-CM in mild-to-moderate AD. Methods: We designed a phase trial that was open-label, single-arm; nine patients (4 males, 5 females; aged 65-89) with mild-to-moderate AD took part. Participants received intranasal WJMSC-CM at escalating s (1.2, 1.8 and 3.0 mL/day) over three consecutive days. Daily vital signs, physical checks and adverse checks were conducted to assess adverse. Baseline and 3-month brain MRI were used to test structural neuroanatomical safety. The baseline and day 4 serum biomarkers (IL-1β, IL-6, TNF-α, CRP, TGF-β, BDNF) were quantitatively determined by ELISA. The MMSE, MoCA, ADL, and IADL scales were used to assess cognitive and functional statuses. Results: All nine patients finished both parts of the study. No major side effects or neuroimaging abnormalities were found. The side effects of two people in the medium group were mild and temporary-cough and tingling of the lips- went away on their own. No significant decrease in pro-inflammatory cytokines was found from serum biomarker analysis (IL-6, TNF-α, IL-1β, CRP; p > 0.05). Interestingly, BDNF levels increased significantly (p = 0.01), mainly in the low- cohort. Although this study was not powered to prove efficacy, exploratory analyses indicated numerical improvements for the treatment group. There was a trend for improvement in cognitive and functional scores during follow up. The results of this study should be interpreted with care, as they may be hypotheses under test and need to be confirmed by properly powered studies. Conclusion: After the experiments, we determined that the WJMSC-CM could be safely administered via the nasal route. Patients with mild and moderate Alzheimer's had no major problems with it. These initial results indicate possible biological activity and warrant further investigation. Further investigation in larger RCTs to assess clinical efficacy.</div> Alzheimer's Disease, Mesenchymal Stem Cells, Conditioned Medium, Intranasal Administration, Safety, Phase I Clinical 0 0 http://bcn.iums.ac.ir/browse.php?a_code=A-10-8588-1&slc_lang=en&sid=1 Setareh Akbari setarehakbari.neuro@gmail.com 13700319475328460059202 13700319475328460059202 No Department of Neuroscience, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran Mostafa Almasi-Dooghaee a_mostafa108@yahoo.com 13700319475328460059203 13700319475328460059203 No Department of Neurology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Alireza Amanollahi Amanollahi.A@gmail.com 13700319475328460059204 13700319475328460059204 No Trauma and Injury Research Center, Critical Care Department, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Mohammad Taghi Joghataei mt.joghataei@yahoo.com 13700319475328460059205 13700319475328460059205 No Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran Saeed Oraee-Yazdani saeed.o.yazdani@gmail.com 13700319475328460059206 13700319475328460059206 No Functional Neurosurgery Research Center, Research Institute of Functional Neurosurgery, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran, Iran Alireza Zali alirezansmd@gmail.com 13700319475328460059207 13700319475328460059207 No Functional Neurosurgery Research Center, Research Institute of Functional Neurosurgery, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran, Iran Soraya Mehrabi soraya.mehrabi@gmail.com 13700319475328460059208 13700319475328460059208 No Department of Neuroscience, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran Naser Amini Amini_ot@yahoo.com 13700319475328460059209 13700319475328460059209 Yes Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran